Research in the Section on Geriatric Psychiatry (SGP) has focused on three main areas: clinical studies of depression and Alzheimer's disease (AD), the pharmacologic modelling of cognition, and the underlying mechanisms of neurodegeneration in AD. With treatment-resistant elderly depressives, work has been published showing that selegiline, a monoamine oxidase inhibitor known mostly for its usefulness with Parkinson's disease, is also effective with older depressives, but only at high doses which inhibit both the MAO-A as well as the MAO-B subtype of the enzyme. In an innovative study of AD patients and age-matched controls, cerebral perfusion and muscarinic receptor labelling was tested with single photon emission computerized tomography (SPECT) scans before and after scopolamine was administered chronically, and it was determined that AD subjects revealed divergent responsivity when compared to the controls. Specifically, the chronic scopolamine treatment led to evidence of increased perfusion in the elderly controls whereas, the AD subjects showed a significant increase in the ratio of muscarinic binding to perfusion following the drug phase compared to the elderly normals, suggestive of differential cholinergic upregulation in these two groups. In pharmacologic modelling studies with normal elderly subjects, it was demonstrated that manipulation of the cholinergic system with m-CPP, a mixed serotonergic agonist/antagonist, could further exacerbate the deficits generated by anticholinergics alone; however, ondansetron, a 5- HT3 antagonist purported to improve memory in selected animal experiments, was not associated with a dampening of the scopolamine- induced memory impairment. Finally, with respect to the basic mechanisms of AD neurotoxicity, we have discovered that the beta amyloid peptide (abeta) may be a functional growth factor. Operating via a tyrosine kinase mediated pathway, abeta regulates processes as diverse as platelet aggregation and neurite outgrowth. Low levels of abeta are soluble and can utilize this mechanism while higher levels tend to aggregate and produce toxicity. APO E modulates abeta formation with the various APO E isozymes acting differently in this process. Further characterization of these mechanisms may well lead to novel strategies for blocking abeta toxicity in vitro and eventually in clinical experiments with AD subjects.